{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T13:08:11Z","timestamp":1788872891487,"version":"build-2803163510"},"reference-count":103,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aim<\/jats:title>\n                    <jats:p>Rheumatoid arthritis (RA) is a chronic joint disease with synovial inflammation and joint damage. Previous studies have shown that polyphyllin VII (PP7) has strong anti\u2010inflammatory activity. However, whether PP7 has anti\u2010RA activity is still unknown. This study aimed to explore the anti\u2010RA effect of PP7 using the adjuvant\u2010induced arthritis (AIA) rat model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Procedure<\/jats:title>\n                    <jats:p>To evaluate the possible protective effect of PP7 against RA, we established an AIA rat model. The inhibitory effects of PP7 on oxidative stress and inflammation were evaluated using commercial kits and\/or RT\u2010PCR. The expression level of ribonucleotide reductase regulatory subunit M2 (RRM2) was determined by western blotting. To explore the mechanisms by which PP7 exerted the protective effect against RA, a cellular inflammatory model using fibroblast\u2010like synoviocytes (FLSs) was established.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>Administration of PP7 alleviated paw swelling and decreased the histological score of paw tissues. PP7 reduced oxidative stress and inflammation in the paw ankle tissues of AIA rats. In FLSs, PP7 also prevented the TNF\u2010\u03b1\u2010induced oxidative stress and inflammatory responses. Notably, mechanism studies demonstrated that RRM2 was a downstream molecule of PP7. Overexpression of RRM2 attenuated the protective effect of PP7 on TNF\u2010\u03b1\u2010stimulated FLSs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>Our results showed that PP7 exerted anti\u2010RA activity through inhibition of oxidative stress and inflammatory responses via modulating RRM2 expression. These findings provided evidence that PP7 might be a promising agent for the treatment of RA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ptr.70271","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T06:39:51Z","timestamp":1771396791000},"page":"2533-2550","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Polyphyllin\n                    <scp>VII<\/scp>\n                    Alleviates Rheumatoid Arthritis by Reducing Oxidative Stress and Inflammation Through Downregulation of Ribonucleotide Reductase Regulatory Subunit\n                    <scp>M2<\/scp>\n                    Expression"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1822-2501","authenticated-orcid":false,"given":"Jiliang","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Ningbo Medical Center Lihuili Hospital The Affiliated Lihuili Hospital of Ningbo University  Ningbo China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Ningbo Medical Center Lihuili Hospital The Affiliated Lihuili Hospital of Ningbo University  Ningbo China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoping","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Ningbo Medical Center Lihuili Hospital The Affiliated Lihuili Hospital of Ningbo University  Ningbo China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Ningbo Medical Center Lihuili Hospital The Affiliated Lihuili Hospital of Ningbo University  Ningbo China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Ningbo Medical Center Lihuili Hospital The Affiliated Lihuili Hospital of Ningbo University  Ningbo China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangliang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Ningbo No. 2 Hospital  Ningbo China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"You","sequence":"additional","affiliation":[{"name":"Biobank, Ningbo Medical Center Lihuili Hospital The Affiliated Lihuili Hospital of Ningbo University  Ningbo China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,17]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27860"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.13818"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.job.2022.12.002"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0303593"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph18081152"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2022-070856"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2022.11542"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.11839"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/480S82a"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/08923973.2018.1434793"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.113560"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.medcli.2023.07.014"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1142\/S0192415X24500368"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/6670464"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics17010045"},{"issue":"10","key":"e_1_2_11_17_1","first-page":"591","article-title":"Global Epidemiology of Rheumatoid Arthritis","volume":"18","author":"Finckh A.","year":"2022","journal-title":"Nature Reviews Rheumatology"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/08830185.2016.1269175"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo14080427"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-020-02004-x"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph17111504"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36625-7"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-025-03096-5"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1155\/mi\/1995952"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-025-10769-9"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2025.107787"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2019.112230"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.24976\/Discov.Med.202436186.134"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.686155"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.70085"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2025.08.032"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1875-5364(25)60855-7"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/350209"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/03009742.2019.1602164"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1080\/08916934.2021.1963959"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-023-04905-z"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.12701\/jyms.2022.00773"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu17091603"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2025.02.002"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(21)00013-8"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2025.157299"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2025.1658089"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.103080"},{"issue":"3","key":"e_1_2_11_44_1","first-page":"2159","article-title":"Silencing RRM2 Inhibits Multiple Myeloma by Targeting the Wnt\/\u03b2\u2010Catenin Signaling Pathway","volume":"20","author":"Liu X.","year":"2019","journal-title":"Molecular Medicine Reports"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/wrr.12939"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2011.07593.x"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-020-01371-1"},{"issue":"5","key":"e_1_2_11_48_1","first-page":"125","article-title":"Inflammatory and Oxidative Stress Markers\u2010Mirror Tools in Rheumatoid Arthritis","volume":"8","author":"Mititelu R. R.","year":"2020","journal-title":"Biomedicine"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13317-020-00145-x"},{"issue":"8","key":"e_1_2_11_50_1","article-title":"Effect of Leflunomide\u2010Metal Complexes on ROS, TNF, and Brain Indolamines in Comparison With Anti\u2010Depressants as Adjunct Therapy in Rheumatoid Arthritic Model","volume":"11","author":"Naeem A.","year":"2023","journal-title":"Biomedicine"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-020-0413-5"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/1805635"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-022-04492-3"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-024-03343-4"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.83682"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.101927"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-025-05526-4"},{"issue":"1","key":"e_1_2_11_58_1","first-page":"25","article-title":"Polyphyllin VII Suppresses Cell Proliferation, the Cell Cycle and Cell Migration in Colorectal Cancer","volume":"21","author":"Song C.","year":"2021","journal-title":"Oncology Letters"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.3390\/nano14070645"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.663"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22084002"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-023-01238-5"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2022.e08982"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1532518"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-21674-6"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2022.102304"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-022-01779-x"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2503785122"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.114958"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02091"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202303167"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.17300"},{"issue":"5","key":"e_1_2_11_73_1","first-page":"2393","article-title":"An Enhanced RRM2 siRNA Delivery to Rheumatoid Arthritis Fibroblast\u2010Like Synoviocytes Through a Liposome\u2010Protamine\u2010DNA\u2010siRNA Complex With Cell Permeable Peptides","volume":"42","author":"Wang X.","year":"2018","journal-title":"International Journal of Molecular Medicine"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1875-5364(21)60107-3"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2021.114368"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1135384"},{"issue":"11","key":"e_1_2_11_77_1","first-page":"2109","article-title":"Identification of RRM2 in Peripheral Blood Mononuclear Cells as a Novel Biomarker for the Diagnosis of Rheumatoid Arthritis","volume":"40","author":"Wu B.","year":"2022","journal-title":"Clinical and Experimental Rheumatology"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.70186"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1387311"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-023-01445-7"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000044384"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568009623666221024103834"},{"key":"e_1_2_11_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2020.113631"},{"key":"e_1_2_11_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110316"},{"key":"e_1_2_11_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1875-5364(25)60823-5"},{"key":"e_1_2_11_86_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01395"},{"key":"e_1_2_11_87_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24010146"},{"key":"e_1_2_11_88_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-016-1036-x"},{"key":"e_1_2_11_89_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24050875"},{"key":"e_1_2_11_90_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13020-021-00447-w"},{"key":"e_1_2_11_91_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S524871"},{"key":"e_1_2_11_92_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1619776"},{"key":"e_1_2_11_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2009.08.020"},{"key":"e_1_2_11_94_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1164157"},{"key":"e_1_2_11_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115516"},{"key":"e_1_2_11_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2021.120204"},{"key":"e_1_2_11_97_1","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185X.15376"},{"key":"e_1_2_11_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.burns.2020.03.012"},{"key":"e_1_2_11_99_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-13-1094"},{"key":"e_1_2_11_100_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-020-3077-z"},{"key":"e_1_2_11_101_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12010-022-04091-4"},{"key":"e_1_2_11_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2014.11.008"},{"key":"e_1_2_11_103_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568009622666220304110222"},{"key":"e_1_2_11_104_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2022.11.022"}],"container-title":["Phytotherapy Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.70271","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ptr.70271","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.70271","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:24:17Z","timestamp":1788870257000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.70271"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,17]]},"references-count":103,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/ptr.70271"],"URL":"https:\/\/doi.org\/10.1002\/ptr.70271","archive":["Portico"],"relation":{},"ISSN":["0951-418X","1099-1573"],"issn-type":[{"value":"0951-418X","type":"print"},{"value":"1099-1573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,17]]},"assertion":[{"value":"2025-07-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}